Sub-Optimal Adherence With Daily Growth Hormones Increases With Each Year of Treatment in a US Commercial Claims Database

Abstract Introduction and Objective: Pediatric growth hormone deficiency (pGHD) occurs in approximately 1 in 4,000 children. The main manifestation is short stature managed with daily injections of somatropin, a recombinant human growth hormone (r-hGH). Prior research has shown that children with good adherence with r-hGH have significantly greater linear growth compared to those with sub-optimal adherence. While previous studies have found sub-optimal adherence with daily r-hGH injectables among children with pGHD, to date, r-hGH adherence has not been studied among large, usual-care populations using validated measurements of adherence. We describe adherence to somatropin treatment over 4 years in a population-based study. Materials and Methods: A retrospective cohort analysis of commercially insured patients ≥3 and <16 years, diagnosed with pGHD, newly treated with somatropin from 01 January 2002 through 31 December 2019 (study time period) was conducted using Optum De-identified Clinformatics Data Mart database. Index date was defined as the first prescription for somatropin between 01 July 2002 to 30 September 2019. Four patient cohorts were identified (12, 24, 36, and 48 months of post-index continuous enrollment). The demographic and clinical profiles of children with pGHD treated with daily injections of somatropin who have good adherence and those with sub-optimal adherence were characterized. Good adherence was defined as medication possession ratio (MPR) of ≥ 80%, sub-optimal adherence as MPR <80%. Logistic regression models will evaluate the relationship between demographic characteristics (age, gender, race/ethnicity) and adherence (good vs. sub-optimal). Results: Patient characteristics were similar across each cohort; in the 12-month cohort (n=3091), mean age was 11.34 ±2.89 years, 75.9% were male, 70.9% white, 9.4% Hispanic, 3.6% Asian, and 3.1% black. At 48 months, 1193 (38.6%) of the 12-month cohort remained for follow-up. At 12 months, 80.1% had good adherence and mean (95% CI) MPR was 0.89 (0.88-0.89) while mean (95% CI) MPR at 48 months was 0.82 (0.81-0.83). The proportion with good adherence at months 24, 36, and 48 were 70.2%, 65.6%, and 64.0%, respectively. Adherence was not associated with age or gender. Blacks and Hispanics consistently exhibited lower adherence. At 12 months, good adherence was observed among 85.7% of Asians, 80.0% of whites, 77.2% of Hispanics, and 76.0% of blacks; at 48 months, good adherence was observed among 73.9% of Asians, 65.4% of whites, 56.8% of blacks, and 55.2% of Hispanics. Logistic regression model results will be provided. Conclusion: Although the majority of children with pGHD demonstrated good adherence with a daily r-hGH regimen, sub-optimal adherence increases with treatment duration and is higher among black and Hispanic children. Strategies that facilitate good adherence to r-hGH may support improved clinical outcomes.

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CT-Determined Body Composition Changes with Recombinant Human Growth Hormone Treatment to Adults with Growth Hormone Deficiency

Human Body Composition ◽

10.1007/978-1-4899-1268-8_53 ◽

1993 ◽

pp. 229-231 ◽

Cited By ~ 1

Author(s):

Lars Lönn ◽

Henry Kvist ◽

Ulla Grangård ◽

Bengt-Åke Bengtsson ◽

Lars Sjöström

Keyword(s):

Growth Hormone ◽

Body Composition ◽

Growth Hormone Deficiency ◽

Human Growth Hormone ◽

Growth Hormone Treatment ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Hormone Treatment ◽

Hormone Deficiency ◽

Composition Changes

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Low FT4 Concentrations around the Start of Recombinant Human Growth Hormone Treatment: Predictor of Congenital Structural Hypothalamic-Pituitary Abnormalities?

Hormone Research in Paediatrics ◽

10.1159/000486033 ◽

2018 ◽

Vol 89 (2) ◽

pp. 98-107 ◽

Cited By ~ 5

Author(s):

Laura van Iersel ◽

Hanneke M. van Santen ◽

Gladys R.J. Zandwijken ◽

Nitash Zwaveling-Soonawala ◽

Anita C.S. Hokken-Koelega ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Hormone Treatment ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Gh Treatment ◽

Central Hypothyroidism ◽

Pituitary Disease

Background: Growth hormone (GH) treatment may unmask central hypothyroidism (CeH). This was first observed in children with GH deficiency (GHD), later also in adults with GHD due to acquired “organic” pituitary disease. We hypothesized that newly diagnosed CeH in children after starting GH treatment for nonacquired, apparent isolated GHD points to congenital “organic” pituitary disease. Methods: Nationwide, retrospective cohort study including all children with nonacquired GHD between 2001 and 2011 in The Netherlands. The prevalence of CeH, hypothalamic-pituitary (HP) abnormalities, and neonatal congenital hypothyroidism screening results were evaluated. Results: Twenty-three (6.3%) of 367 children with apparent isolated GHD were prescribed LT4 for presumed CeH within 2 years after starting GH treatment. Similarly to children already diagnosed with multiple pituitary hormone deficiency, 75% of these 23 had structural HP abnormalities. In children not prescribed LT4, low pre- or post-GH treatment FT4 concentrations were also associated with structural HP abnormalities. Neonatal screening results of only 4 of the 23 children could be retrieved. Conclusion: In children with nonacquired, apparent isolated GHD, a diagnosis of CeH after, or a low FT4 concentration around the start of GH treatment, is associated with congenital structural HP abnormalities, i.e., “organic” pituitary disease. Neonatal values could not be judged reliably.

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The Angle of Trunk Rotation in Children With Growth Hormone Deficiency

10.21203/rs.3.rs-70130/v1 ◽

2020 ◽

Author(s):

Magdalena Kobylińska ◽

Roksana Ewa Malak ◽

Katarzyna Majewska ◽

Włodzimierz Samborski ◽

Andrzej Kędzia

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Human Growth Hormone ◽

Bone Structure ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Hormone Deficiency ◽

Trunk Rotation ◽

Sport Activities ◽

Rhgh Treatment

Abstract Background. Growth hormone plays a vital role in the human body. Its deficiency can lead to numerous disorders, including musculoskeletal system defects. Treatment with recombinant human growth hormone (rhGH) in children suffering from growth hormone deficiency (GHD) increases muscle mass and improves bone structure.Aim. The purpose of this study was to evaluate the angle of trunk rotation (ATR) in patients diagnosed with GHD treated with rhGH and to observe the incidence of scoliosis.Material and Methods. The study was conducted among 50 children diagnosed with GHD. The group consisted of 11 girls and 39 boys aged 6-16. The study group included 50 children: 10 children just qualified for rhGH treatment and 40 patients undergoing this treatment, with different therapy duration. ATR was measured using a Bunnell scoliometer on five levels of the spine: cervical 7 / thoracic 1, thoracic 6, thoracic 12 / lumbar 1, lumbar 3, lumbar 5 / sacral 1.Results. The most numerous asymmetries among the examined group were in the thoracolumbar segment and at the thoracic 6 level. Girls had greater asymmetries compared to boys especially at thoraco – lumbar and lumbar 3 level. There were no statistically significant differences in ATR at any level comparing patients before hormonal treatment and patients undergoing rhGH treatment. The age of the beginning of the therapy, the duration of rhGH therapy, and body mass index (BMI) also had no effect on ATR. Sport activities had a positive impact on the results obtained by scoliometer assessment.Conclusions. The angle of trunk rotation is higher in growth hormone-deficient females than in males. Weight, height, BMI, the time of growth hormone therapy beginning and the duration of this therapy do not influence ATR. The more sport activities, the lower value of the angle of trunk rotation, especially in male patients. Obtained results support the thesis, that treatment with recombinant human growth hormone does not increase the incidence of scoliosis.

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Comparison of the efficacy and safety of recombinant human growth hormone in treating idiopathic short stature and growth hormone deficiency in children

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2020.101331 ◽

2020 ◽

Vol 53-54 ◽

pp. 101331

Author(s):

Ling Hou ◽

Yan Liang ◽

Wei Wu ◽

Han-Hua Lin ◽

Xiao-Ping Luo ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Human Growth Hormone ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Idiopathic Short Stature ◽

Hormone Deficiency ◽

Efficacy And Safety

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Validating genetic markers of response to recombinant human growth hormone in children with growth hormone deficiency and Turner syndrome: the PREDICT validation study

Acta Endocrinologica ◽

10.1530/eje-16-0357 ◽

2016 ◽

Vol 175 (6) ◽

pp. 633-643 ◽

Cited By ~ 6

Author(s):

Adam Stevens ◽

Philip Murray ◽

Jerome Wojcik ◽

John Raelson ◽

Ekaterina Koledova ◽

...

Keyword(s):

Growth Hormone ◽

Random Forest ◽

Growth Hormone Deficiency ◽

Genetic Markers ◽

Validation Study ◽

Growth Response ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Hormone Deficiency ◽

First Year

Objective Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations. Design and methods Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification. Results The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes – SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR). Conclusions The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use.

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